Hauser G J, Myers A K, Dayao E K, Zukowska-Grojec Z
Division of Pediatric Critical Care Medicine, Georgetown University Children's Medical Center, Washington, DC.
Am J Physiol. 1993 Oct;265(4 Pt 2):H1416-23. doi: 10.1152/ajpheart.1993.265.4.H1416.
Neuropeptide Y (NPY), a sympathetic and platelet-derived vasoconstrictor, acts both directly and by potentiating adrenergic responsiveness and therefore may be beneficial in endotoxic shock, where suppressed vascular responsiveness to adrenergic agents is a key factor. This was studied in anesthetized rats. First, infusion of a nonhypotensive dose of endotoxin (lipopolysaccharide, LPS) markedly suppressed the pressor response to increasing doses of norepinephrine (NE), angiotensin II, and vasopressin but did not suppress the response to NPY. Second, in rats rendered hypotensive by intravenous LPS, continuous NE infusion (0.1-1.0 microgram.kg-1 x min-1 started 5 min after LPS for 1 h) did not alter hemodynamics. In contrast, 5 nmol.kg-1 x min-1 of NPY (equipotent to 0.1 microgram.kg-1 x min-1 of NE in normal rats) increased mean arterial pressure (MAP, from 64 to 114% of baseline), total peripheral resistance index (TPRI, from 64 to 154% of baseline), and left ventricular stroke work index (from 36 to 73% of baseline), without changing cardiac index (CI). Third, in a similar experimental protocol, pretreatment of the hypotensive rats with phentolamine blocked the pressor effect of NE infusion, but only partially attenuated the response to NPY. Finally, addition of low-dose NPY to NE infusion improved survival following a lethal dose of LPS compared with treatment with NE alone (P < 0.01). Thus, unlike other vasoconstrictors tested, NPY-mediated vasoconstriction is preserved during endotoxemia. The beneficial effect of NPY is mediated by increased TPRI without reduction in CI; both NPY receptor-mediated vasoconstriction and potentiation of adrenergic responsiveness may be involved.
神经肽Y（NPY）是一种由交感神经和血小板产生的血管收缩剂，它既能直接发挥作用，又能增强肾上腺素能反应，因此在内毒素休克中可能有益，在内毒素休克中，血管对肾上腺素能药物的反应性受到抑制是一个关键因素。本研究在麻醉大鼠中进行。首先，输注非低血压剂量的内毒素（脂多糖，LPS）可显著抑制对递增剂量去甲肾上腺素（NE）、血管紧张素II和血管加压素的升压反应，但不抑制对NPY的反应。其次，在静脉注射LPS导致低血压的大鼠中，持续输注NE（0.1 - 1.0微克·千克⁻¹·分钟⁻¹，在LPS注射后5分钟开始，持续1小时）并未改变血流动力学。相比之下，5纳摩尔·千克⁻¹·分钟⁻¹的NPY（在正常大鼠中与0.1微克·千克⁻¹·分钟⁻¹的NE等效）可提高平均动脉压（MAP，从基线的64%升至114%）、总外周阻力指数（TPRI，从基线的64%升至154%）和左心室每搏功指数（从基线的36%升至73%），而不改变心脏指数（CI）。第三，在类似的实验方案中，用酚妥拉明预处理低血压大鼠可阻断NE输注的升压作用，但仅部分减弱对NPY的反应。最后，与单独用NE治疗相比，在NE输注中添加低剂量NPY可提高致死剂量LPS后的存活率（P < 0.01）。因此，与其他测试的血管收缩剂不同，在内毒素血症期间，NPY介导的血管收缩作用得以保留。NPY的有益作用是通过增加TPRI而不降低CI来介导的；可能涉及NPY受体介导的血管收缩和肾上腺素能反应的增强。
